Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy.

in The New England journal of medicine by Christine E Brown, Darya Alizadeh, Renate Starr, Lihong Weng, Jamie R Wagner, Araceli Naranjo, Julie R Ostberg, M Suzette Blanchard, Julie Kilpatrick, Jennifer Simpson, Anita Kurien, Saul J Priceman, Xiuli Wang, Todd L Harshbarger, Massimo D'Apuzzo, Julie A Ressler, Michael C Jensen, Michael E Barish, Mike Chen, Jana Portnow, Stephen J Forman, Behnam Badie

TLDR

  • A patient with a type of brain tumor called glioblastoma received special cells called CAR-engineered T cells that were designed to target a specific protein on the tumor. The cells were infused into the patient's brain and showed that they were safe and effective in treating the tumor. The study suggests that CAR T-cell therapy could be used as a treatment option for other types of brain tumors.

Abstract

A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)-engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2). Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes - infusions into the resected tumor cavity followed by infusions into the ventricular system. Intracranial infusions of IL13Rα2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher. After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. This clinical response continued for 7.5 months after the initiation of CAR T-cell therapy. (Funded by Gateway for Cancer Research and others; ClinicalTrials.gov number, NCT02208362 .).

Overview

  • The study focused on the use of chimeric antigen receptor (CAR)-engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2) in a patient with recurrent multifocal glioblastoma. The hypothesis being tested was whether CAR T-cell therapy would be safe and effective in treating the patient's tumors. The methodology used for the experiment involved multiple infusions of CAR T cells administered over 220 days through two intracranial delivery routes - infusions into the resected tumor cavity followed by infusions into the ventricular system. The primary objective of the study was to evaluate the safety and efficacy of CAR T-cell therapy in treating the patient's tumors.

Comparative Analysis & Findings

  • The study compared the outcomes observed under different experimental conditions or interventions, specifically the intracranial infusions of IL13Rα2-targeted CAR T cells versus no treatment. The results showed that intracranial infusions of IL13Rα2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher. After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. This clinical response continued for 7.5 months after the initiation of CAR T-cell therapy.

Implications and Future Directions

  • The study's findings suggest that CAR T-cell therapy targeting IL13Rα2 is safe and effective in treating recurrent multifocal glioblastoma. The study's results also highlight the potential for CAR T-cell therapy to be used as a treatment option for other types of brain tumors. Future research directions could include expanding the use of CAR T-cell therapy to other types of brain tumors and exploring the use of different CAR T-cell targets.
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